The estimated incidence of prostate cancer in men over the age of 50 is 30%, making it the most common form of cancer among males. Currently, prostate cancer is the second leading cause of cancer death among men in the United States.
Although a considerable amount of research has been devoted to developing effective therapies against the disease, prostate cancer remains difficult to treat. The most common forms of treatment remain based on surgery, radiation therapy, or a combination of surgery and radiation therapy. However, these methods are ineffective in a significant number of cases and have a great many deleterious side effects.
Two previously identified prostate specific proteins, prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), have been identified and used as markers for identifying patients with or at risk for prostate cancer. The therapeutic and diagnostic potential of PSA and PAP, however, is limited. For example, PSA levels do not always correlate with the presence of prostate cancer. In some cases, elevated PSA levels are associated with a number of non-prostate cancer disorders, including benign prostatic hyperplasia (BPH). Furthermore, PSA measurements correlate with prostate volume, an unreliable marker for prostate cancer, and do not indicate the level of metastasis.
Besides serum markers, such as PSA, physicians recommend the digital rectal examination (DRE) for aging men, particularly men over the age of 50 or who have a family history of prostate cancer. The sensitivity of the DRE is limited, because the examining finger can only palpate the posterior and lateral portions of the gland, leaving some tumors undetected. If a DRE or serum marker test is abnormal, imaging tools, such as MRI or transrectal ultrasound must be used to further examine the gland. However, cancer is confirmed only by a biopsy.
Pathologists in the United States primarily use the Gleason system to assign as grade to tumors detected in biopsies. The Gleason system involves histologic grading based on the pattern of glandular formation, assigning a number of 1 to 5. Lower numbers are well differentiated and higher numbers are poorly differentiated (Gleason and Mellinger, 1974, J. Urol. 111:58–64). A pathologist assigns one number based on the level of differentiation of the most prevalent grade in the sample, and makes a second assessment based on the predominant secondary grade. The two grades are added together to get the “Gleason sum.” While the Gleason system is widely used, it often leads to variable scores between different diagnosticians. Poor reproducibility between diagnosticians is a major problem in grading prostate tumors.
The screening methods for detecting and diagnosing prostate tumors discussed above are limited in their sensitivity. Consequently, there is a need in the art for improved methods of diagnosing prostate cancer. Given the discrepancy between pathologists in grading the severity of tumors, there also remains a need for an easier, more accurate method of grading prostate tumors.